Alcaptonuria Explained

What is Alkaptonuria?

Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones.

Alkaptonuria (AKU) is a rare disease, which causes severe, early-onset osteoarthritis. It can be a painful and degenerative disease. Other names for AKU include Black Bone Disease or black urine disease.

Alkaptonuria is caused by the lack of an enzyme called homogentisic dioxygenase (HGD). This leads to a condition in which patients cannot fully break down a toxic acid called homogentisic acid, or HGA. Although some HGA is eliminated in urine, a large amount builds up in the body. This accumulates at 2,000 times the normal rate, leading to severely debilitating health problems. Black urine is a common symptom of AKU and is often used as a diagnostic tool.

The accumulation of HGA causes discolouration of bone and cartilage in a process called ochronosis. Black and brittle cartilage is more susceptible to the normal wear and tear that occurs in the body, quickly leading to painful movements in the joints. As the cartilage degrades over time, bones rub against one another, causing painful osteoarthritis. AKU has also been linked to heart disease and related heart complications. A build-up of HGA causes the vessels and valves to harden, making them less effective at managing the flow of blood around the body.

How is alkaptonuria inherited?

Alkaptonuria is caused by a genetic mutation. It is a recessive disorder, meaning that the AKU gene must be passed on by both of the patient’s parents. People with one copy of the gene are known as carriers of the disease; they do not suffer from the disease, but are at risk of passing the gene on to their children. If both parents are carriers, their child has a 25% chance of developing AKU.

Does alkaptonuria affect children?

AKU patients are born with the disease. However, with the exception of black urine, none of the symptoms present until patients reach their 20s. The reasons for this are unclear and this is one area that our research teams are focusing on. It is assumed that HGA levels accumulate during childhood.

How common is alkaptonuria?

AKU is a rare disease with an estimated frequency of one in 250,000 to one in 500,000. In the UK, we currently only know of 64 patients.

There are some countries where AKU seems to be more common. One is Slovakia, where it is estimated to affect one person in 19,000. Our teams have identified more than 250 patients in this one country to date. This may be the result of the isolated community which lives in North Slovakia.

Are men and women affected equally?

AKU affects both men and women in equal numbers. However, symptoms appear in women on average 5-10 years later than in men. Women’s protection against developing AKU symptoms seems to diminish after the menopause, suggesting an important role for female hormones.